Children born with a head circumference below the 3rd percentile are at increased risk of cognitive and other neurologic handicaps. This has led to the view that congenital microcephaly is an indicator of disturbed brain growth and development in utero. No previous study has evaluated potential risk factors of congenital microcephaly. This proposal has two components, one concerned with antecedents and one with clinical correlates of congenital microcephaly. In the first component, a case-control study of congenital microcephaly, the cases will be newborns whose head circumference is more than 2 standard deviations below the mean for gestational age and who have no obvious congenital malformation or evident explanation for their microcephaly. Hypotheses to be evaluated have been drawn from the literature about antecedents of delayed myelination, white matter injury, intrauterine growth retardation, as well as from case reports of human microcephaly and studies in laboratory animals of factors associated with reduced brain weight at birth. The second component has been designed to determine to what extent babies with intrauterine brain growth retardation manifest "perinatal distress." If babies with congenital microcephaly are more likely than their peers to display ominous fetal heart patterns, low Apgar scores and need for ventilatory assistance, then these perinatal problems might reflect preexisting disturbances rather than indicating intranatal hypoxic-ischemic brain damage. Such findings would influence hypotheses about the timing of brain damage in human newborns, and might also contribute to reducing the obstetric malpractice crisis. In the second component, the cohort of all newborns with congenital microcephaly born at one hospital during a two-year interval (i.e., the cases from component 1 plus microcephalic babies who were excluded from component 1) will be compared to their peers (including the controls from component 1). The null hypothesis to be tested is: Babies with preexisting neurologic aberration, as manifested by congenital abnormality in the occurrence of such perinatal disturbances as ominous fetal heart patterns, meconium staining of the amniotic fluid, low Apgar scores, and need for feeding and ventilatory assistance.